Serial 1H-MRS in relapsing-remitting multiple sclerosis: effects of interferon-β therapy on absolute metabolite concentrations

Abstract

To assess the applicability of magnetic resonance spectroscopy (MRS) for long-term follow-up of neurological diseases a longitudinal 1H-MRS study at 3 T was carried out on ten patients having relapsing-remitting multiple sclerosis (MS) who, after baseline examination, received interferon-beta (IFN) 1b. At 8-20 examinations within up to 34 months absolute concentrations of N-acetylaspartate (NAA), total creatine (tG), and choline-containing compounds (tCho) were determined in a large non-enhancing lesion and contralateral normal appearing white matter (NAWM). MR spectra were analyzed using a novel time domain-frequency domain method including non-parametric background characterization. For comparison at baseline, ten healthy controls were examined. The concentrations of tCho and tCr were found to be higher in MS brain than in control brain. Besides a non-significantly lower NAA concentration in lesions there were no concentration differences between lesions and NAWM. Over the follow-up period the measured metabolite concentrations exhibited a high variability. Most concentrations remained within this scatter, and statistical tests revealed significant fluctuations in the levels of metabolites in one case only. This stability of the metabolite concentrations over time might result from IFN therapy as for the spontaneous course of relapsing-remitting MS decreasing metabolite (NAA/tCr) ratios have been reported. The results further suggest that future treatment trials intending to use metabolite concentrations as a secondary outcome indicator use even longer observation periods and, besides group analysis of large cohorts, investigate the time behavior of selected single cases. The biochemical abnormalities found in NAWM emphasize the importance of analyzing both lesion and NAWM.

Time-domain semi-parametric estimation based on a metabolite basis set

“…In that case, the model function iŝ x xðp; Þ ¼x x Met ðpÞ þb bðÞ ð 4Þ whereb bðÞ is the mathematical model function of the background and is the nuisance parameter vector mentioned above. This was done in the frequency-domain 7,9,34,35 and in the time-domain. 36,37 Often, a penalization term is added in equation (4).…”

MR Spectroscopy in Multiple Sclerosis - A New Piece of the Puzzle or Just a New Puzzle

“…Very often neurological symptoms may occur without any (correlating) acute enhancing MRI lesions, especially in the spinal cord. And most confusing is that acute enhancing MRI lesions that are clinically silent, may be found between relapses, even though they are located in eloquent areas (Davie et al, 1994;Schubert et al, 2002).…”

Imaging of multiple sclerosis: Role in neurotherapeutics

“…While highly attractive, the technical demands of spectroscopy have generally limited its use in therapeutic trials to single centers with conflicting results generally reported from small patient cohorts. IFNB has shown conflicting results on MRS parameters, including the ability to improve/stabilize 120 or have little effect [121][122][123] on NAA content in MS cohorts. The small size of patient cohorts studied and the lack of parallel control groups likely contribute to these ambiguous results.…”